This application requests funding for an Illumina (Solexa) Genome Analyzer IIx massively parallel sequencer to enhance the capacity and capabilities of the Deep Sequencing Core Laboratory at UMass Medical School. Using a first generation Solexa instrument available in the core facility a number of laboratories have developed methods for mapping functional genomic elements and genomic architecture, identifying populations of small ncRNAs present in various species and cell types, and determining DNA-binding specificities for entire families of DNA-binding domains. The demand for this sequencing service is outstripping the present capacity of our core facility;the number of new users is growing rapidly with NIH-funded projects in areas of human disease such as ALS, Schizophrenia, Diabetes, Cancer and Cardiovascular disease. Addition of another deep sequencing instrument with improved capacity and capabilities is critical to meet the needs of these NIH-funded investigators. Twenty-four NIH funded projects that will directly benefit from this new capacity are described within our application.